脂肪细胞缺氧对骨骼肌细胞胰岛素作用的影响

The effect of hypoxia of adipocytes on insulin function in skeletal muscle cells

目的:观察脂肪细胞缺氧对骨骼肌细胞胰岛素作用的影响。方法:缺氧(5%CO2、85%N2、10%H2或200μmol/LCoCl2)处理小鼠3T3-L1脂肪细胞,制备条件培养基孵育小鼠骨骼肌细胞。通过对胰岛素信号通路中关键蛋白的磷酸化水平和葡萄糖转运子4(GLUT4)转位得以检测骨骼肌胰岛素作用的改变。结果:缺氧处理的3T3-L1脂肪细胞条件培养基抑制骨骼肌胰岛素信号通路,其中胰岛素受体底物1(IRS1 Ser307)磷酸化水平呈显著增高,相反蛋白激酶B(Akt Ser473)磷酸化水平呈显著下降,最终显著抑制了胰岛素刺激的GLUT4myc转位(P<0.05)。结论:抑制胰岛素刺激的GLUT4myc转位,其机制与IRS1的Ser307的磷酸化水平升高和Akt的Ser473的磷酸化水平降低有关。

Objective： To investigate the effect of hypoxia of adipocytes on the insulin function in skeletal muscle cells. Methods： 3T3-L1 adipocytes were treated with hypoxia by incubating at 5% CO2, 85% N2, 10% HE or with 200 μmolL CoCl2. The conditioned medium from 3T3-LI adipocytes was used to incubate skeletal muscle cells. The change of the insulin function was studied by detection of phosphorylation of insulin signal molecules and the translocation of glucose transport 4 （GLUT4）. Results： The conditioned medium from hypoxia-treated 3T3-L1 adipocytes inhibited insulin signaling pathway by increased the phosphorylation of insulin receptor substrate 1 （IRS1 Ser307）, decreased the phosphorylation of protein kinase B （Akt Ser473）, therefore inhibited GLUT4rnyc translocation in response to insulin （P〈0.05）. Conclusion： The conditioned medium from hypoxia-treated adipocytes inhibits insulin function.The mechanism may relate to the increase of phosphorylation of IRSI Set307 and decrease of the phosphorylation Akt 5er473.